Compositions and methods for diagnosing and treating pancreatic cancer

Abstract

The present invention provides compositions and methods for treating and diagnosing the presence of solid tumor stem cells in a patient (e.g., based on the presence of c-Met). In certain embodiments, the presence or absence of solid tumor stem cells (e.g., pancreatic solid tumor stem cells) can be determined through the use of a single cells surface marker (e.g., c-Met). The present invention also provides methods for screening candidate compounds (e.g., c-Met antagonists) for the ability to inhibit the tumorigenisis of pancreatic solid tumor stem cells.

1 . A method of detecting solid tumor stem cells comprising;
 a) providing:
 i) a tissue sample taken from a tumor of a subject, and 
 ii) an antibody, or antibody fragment, specific for the c-Met protein; and 
   b) contacting said tissue sample with said antibody, or antibody fragment, under conditions such that the presence or absence of c-Met+ solid tumor stem cells are detected.   
     
     
         2 . The method of  claim 1 , wherein said antibody, or antibody fragment, is conjugated to a signal molecule. 
     
     
         3 . The method of  claim 2 , wherein said signal molecule comprises a fluorescent molecule. 
     
     
         4 . The method of  claim 2 , wherein said signal molecule comprises an enzyme that can catalyze a color producing reaction in the presence of a colorimetric substrate. 
     
     
         5 . The method of  claim 1 , where said method further comprises contacting said sample with a secondary antibody, or secondary antibody fragment, specific for said antibody or antibody fragment. 
     
     
         6 . The method of  claim 5 , wherein said secondary antibody, or secondary antibody fragment, comprises a signal molecule. 
     
     
         7 . The method of  claim 1 , wherein no other proteins or nucleic acids are assayed in order to determine the presence or absence of said c-Met+ solid tumor stem cells. 
     
     
         8 . The method of  claim 1 , wherein said tumor is a pancreatic tumor. 
     
     
         9 - 15 . (canceled) 
     
     
         16 . An isolated population of cancer stem cells that are:
 a) tumorigenic; and   b) c-Met+.   
     
     
         17 . The isolated population of  claim 16 , wherein said cancer stem cells are pancreatic cancer stem cells. 
     
     
         18 . The isolated population of cancer stem cells of  claim 16 , wherein the population comprises at least 60% cancer stem cells and less than 40% non-tumorigenic tumor cells. 
     
     
         19 . The isolated population of cancer stem cells of  claim 16 , wherein the cancer stem cells: are enriched at least two-fold compared to unfractionated non-tumorigenic tumor cells. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . A method of treating a patient with pancreatic cancer comprising: administering a c-Met inhibitor to said patient such that the number of pancreatic stem cells expressing c-Met is reduced or eliminated in the subject. 
     
     
         23 . The method of  claim 22 , wherein said method further comprises administering a chemotherapeutic selected from the group consisting of: 5-fluorouracil (5-FU); Gemcitabine (Gemzar); and Capecitabine 
     
     
         24 . The method of  claim 22 , wherein said c-Met inhibitor is PHA-665752 or PF-02341066. 
     
     
         25 . The method of  claim 22 , further comprising, prior to said administering, a step of contacting a sample from said patient comprising pancreatic tumor cells with a reagent that binds c-Met. 
     
     
         26 - 32 . (canceled)